Effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) on convulsive seizures

Endothelins (ET-1 and ET-3) are produced in the brain and may act as neuropeptides. The effects of two endothelins (ET-1 and ET-3) were investigated using pentylenetetrazole- (PTZ), strychnine- (STR), picrotoxin- (PIC) and bicuculline-induced (BIC) convulsions. ET-1 did not exert any anticonvulsive effect. ET-3, being more specific for the brain, showed anticonvulsive activity on PTZ and BIC seizures, but not on PIC and STR seizures. Different mechanisms underlie the action of the convulsants. PTZ, BIC and PIC realized their convulsive effects through the GABAergic inhibitory transmitter system; STR exerted an excitatory effect on the spinal cord by blocking the glycine transmitter system. The results suggest that the anticonvulsive effects of ET-3 might be due to an indirect influence on the GABAergic system in the brain.